4-176686027-T-C

Variant names:

• chr4-176686027-T-C
• rs7665213
• NM_005429.5:c.1145+1160A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.1145+1160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,080 control chromosomes in the GnomAD database, including 30,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30840 hom., cov: 33)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 1 publications found

Genes affected

VEGFC (HGNC:12682): (vascular endothelial growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014]

HAFML (HGNC:56694): (HuR (ELAVL1) associated fibroblast migratory lncRNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.1145+1160A>G		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.182+16318T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.1145+1160A>G		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.243+6277T>C		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.155+16318T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95172 AN: 151962 Hom.: 30841 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95211 AN: 152080 Hom.: 30840 Cov.: 33 AF XY: 0.634 AC XY: 47118 AN XY: 74358

African (AFR) AF: 0.458 AC: 18972 AN: 41444

American (AMR) AF: 0.597 AC: 9132 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3660 AN: 5174

South Asian (SAS) AF: 0.738 AC: 3562 AN: 4824

European-Finnish (FIN) AF: 0.752 AC: 7960 AN: 10588

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47386 AN: 67976

Other (OTH) AF: 0.628 AC: 1323 AN: 2108

Alfa AF: 0.645 Hom.: 11190

Bravo AF: 0.604

Asia WGS AF: 0.707 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7665213; hg19: chr4-177607181;